Experimental Investigation and Modeling of Cocrystal Formation in L-Menthol/Thymol Eutectic System

Abstract

Solid–liquid equilibria (SLE) of the l-menthol/thymol eutectic system were studied in detail using a combination of differential scanning calorimetry (DSC) and powder X-ray diffraction (XRD). The existence of two cocrystals with stoichiometric ratios 1:3 and 3:2 for l-menthol:thymol was monitored by performing XRD on samples of different compositions. Moreover, the existence of two solid solution regions of l-menthol in thymol and l-menthol in the 1:3 cocrystal was observed. The nonrandom two-liquid (NRTL) and two-suffix Margules models were applied to model the measured SLE data. The two eutectic points of the system were determined at Te1cal = 271.7 K, xthymol,e1cal = 0.48 and Te2cal = 273.1 K, xthymol,e2cal = 0.33. The complex character of the obtained phase diagram of the system shows that not all deep eutectic systems can be assumed to be of a simple eutectic type with immiscible solid phases. For the accurate determination of the SLE of eutectic systems, a combination of several experimental techniques and thermodynamic modeling is needed.